Suo Yaran, Li Shuyu, Lyu Haining, Zhao Xin, Xing Jiale, Chai Xin, Zhang Qian, Fu Chunjin, Xu Chengchao, Liao Jingjing
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Synth Syst Biotechnol. 2025 Feb 28;10(2):610-619. doi: 10.1016/j.synbio.2025.02.013. eCollection 2025 Jun.
Natural products from medicinal plants serve as an invaluable resource for drug discovery and development. However, low-abundance natural products are often understudied due to the challenges of obtaining sufficient quantities for pharmacological testing in cells or animals. Additionally, their complex stereochemistry and functional groups make chemical synthesis and purification difficult. In this study, we showcased the power of biosynthetic approaches to explore these underexplored compounds, using the low-abundance polyphyllin trillin 6'--glucoside from as an example. We identified two trillin 6'--glucosyltransferases required for its biosynthesis and successfully reconstructed the entire pathway in . We demonstrated that trillin 6'--glucoside exhibits anti-bacterial activity comparable to major polyphyllins like polyphyllins I, II, and VII. Notably, it also showed much lower hemolytic activity, a common side effect of those major polyphyllins. Together, our study underscores the advantages of employing biosynthetic approaches to explore natural products that exist in low or trace abundances yet possess equally important pharmacological activities.
药用植物中的天然产物是药物发现和开发的宝贵资源。然而，由于难以获得足够数量用于细胞或动物药理测试，低丰度天然产物往往研究不足。此外，它们复杂的立体化学和官能团使得化学合成和纯化变得困难。在本研究中，我们以来自[植物名称]的低丰度重楼皂苷三叶苷6'-葡萄糖苷为例，展示了生物合成方法在探索这些未充分研究的化合物方面的强大作用。我们鉴定出了其生物合成所需的两种三叶苷6'-葡萄糖基转移酶，并成功在[宿主名称]中重建了整个途径。我们证明三叶苷6'-葡萄糖苷具有与主要重楼皂苷如重楼皂苷I、II和VII相当的抗菌活性。值得注意的是，它的溶血活性也低得多，而溶血活性是那些主要重楼皂苷常见的副作用。总之，我们的研究强调了采用生物合成方法探索低丰度或痕量存在但具有同等重要药理活性的天然产物的优势。
